<scp>l</scp>-Theanine Activates the Browning of White Adipose Tissue Through the AMPK/?-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-Induced Obesity in Mice

l-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice l-theanine (100 mg/kg/day) enhanced adaptive thermogenesis and induced browning inguinal white adipose tissue (iWAT) elevated expression Prdm16, Ucp1, other thermogenic genes. Meanwhile, administration increased energy expenditure. In vitro studies indicated development brown-like features in adipocytes. The shRNA-mediated depletion Prdm16 blunted role promoting phenotypes adipocytes iWAT mice. AMPK? phosphorylation both iWAT. Knockdown abolished l-theanine–induced upregulation adipocyte browning. ?-ketoglutarate (?-KG) level adipocytes, which may increase transcription by inducing active DNA demethylation on its promoter. AMPK activation was required for ?-KG Moreover, ameliorated obesity, improved glucose tolerance insulin sensitivity, reduced plasma triglyceride, total cholesterol, free fatty acids high-fat diet–fed Our results suggest potential combating diet-induced obesity mice, involve WAT.